DIFFERENTIAL METABOLISM OF DIETARY FATTY ACIDS

膳食脂肪酸的差异代谢

• 批准号: 7605805
• 负责人: Craig Lawrence Kien
• 金额: $ 3.21万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605805
• 关键词: 1,2-diacylglycerol; Acyl Coenzyme A; Address; Adipose tissue; Adult; Affect; Age; Biochemical Pathway; Cardiolipins; Carnitine; Computer Retrieval of Information on Scientific Projects Database; Control Groups; Daily; Data; Diabetes Mellitus; Diagnosis; Diet; Dietary Fatty Acid; Diglycerides; Energy Metabolism; Exercise; Fatty Acids; Fatty acid glycerol esters; Food; Funding; Future; Grant; Human; Inborn Genetic Diseases; Institution; Insulin Resistance; Lipids; Masks; Membrane Lipids; Metabolic; Metabolism; Muscle; Non obese; Obesity; Oleic Acid; Oleic Acids; Palmitic Acids; Phospholipids; Prevention; Randomized; Relative (related person); Research; Research Personnel; Resources; Rest; Screening procedure; Skeletal Muscle; Source; Study Subject; Techniques; Tissues; Triglycerides; United States National Institutes of Health; Universities; Work; day; design; fatty acid metabolism; fatty acid oxidation; feeding; human subject; insulin signaling; non-diabetic; novel; oxidation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our Preliminary Data in young, non-obese, human subjects suggest that increasing dietary palmitic acid (PA) over a period of 28-d lowers daily non-resting energy expenditure, blunts the usual post-exercise rise in energy expenditure, and lowers fatty acid (FA) oxidation in the fed state. Conversely, we found that increasing dietary oleic acid (OA) enhances FA oxidation and increases non-resting energy expenditure. However, it is important to determine if this effect can be seen within days of the diet or whether marked changes in membrane lipid composition are required. This question has relevance to the design of future studies, where subjects could be their own control. Also, as a consequence of their opposite effects on fat oxidation, PA and OA may in turn have contrasting effects on intramyocyte lipid concentration, which could affect insulin signaling in that tissue. Recent work at the Duke University Stedman Center by Dr. Muoio and others (1) has shown how metabolic screening (acyl-carnitine and acyl-CoA profiling) can be used both to address hypothesized mechanisms, and to reveal unexpected relationships that prompt new and/or alternative hypotheses. In particular, this work has demonstrated that techniques, previously used to presumptively diagnose inborn errors of FA metabolism, can be used to provide data on particular biochemical pathways that can be altered by changes in the capacity for FA oxidation. As part of an overall plan to gather preliminary data for a related NIH application, submitted on 2/1/05, we will collect muscle tissue for analysis of acyl-carnitine and acyl-CoA by Dr. Muoio at the Stedman Center. To explore these issues, a double-masked randomized, parallel groups, controlled feeding trial (7d) is proposed in 24 healthy, non-obese, adults, 18-40 yr of age examining the effects of two real food diets, differing in the relative concentrations of PA and OA. Two Specific Aims will be carried out: 1. To determine if increasing the PA content of the diet decreases fat oxidation in the fed state compared to a diet with lower PA and much higher OA. 2. To determine if raising the PA content of the diet increases the triacylglycerol (TAG) and diacylglycerol (DAG) content of muscle and alters the cardiolipin content of muscle, the fatty acid composition of phospholipids in muscle and adipose tissue, and the acyl-carnitine and acyl-CoA profile of skeletal muscle. This project will provide novel data in non-obese, non-diabetic humans on the effects of PA and OA, the two most common FA in the diet, on fat oxidation and muscle lipids. This study will have particular relevance to the prevention of insulin resistance, diabetes, and obesity.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们在年轻、非肥胖的人类受试者中的初步数据表明，在28天的时间内增加膳食棕榈酸（PA）可以降低每日非静息能量消耗，减弱通常的运动后能量消耗上升，并降低进食状态下的脂肪酸（FA）氧化。 相反，我们发现，增加膳食油酸（OA）增强FA氧化，增加非静息能量消耗。 然而，重要的是要确定这种影响是否可以在饮食的几天内看到，或者是否需要膜脂质组成的显着变化。 这个问题与未来研究的设计相关，受试者可以自己控制。 此外，由于它们对脂肪氧化的相反作用，PA和OA可能反过来对肌细胞内脂质浓度具有相反的作用，这可能影响该组织中的胰岛素信号传导。 Muoio博士和其他人（1）最近在杜克大学斯特德曼中心的工作表明，代谢筛查（酰基肉毒碱和酰基辅酶A谱）可用于解决假设的机制，并揭示提示新的和/或替代假设的意外关系。特别是，这项工作已经证明，技术，以前用于推定诊断先天性错误的FA代谢，可用于提供特定的生化途径，可以改变的能力FA氧化的数据。 作为收集2005年2月1日提交的相关NIH申请的初步数据的总体计划的一部分，我们将收集肌肉组织，供Stedman中心的Muoio博士分析酰基肉毒碱和酰基CoA。 为了探讨这些问题，在24名18-40岁的健康、非肥胖成年人中进行了一项双盲、随机、平行组、对照喂养试验（7天），检查两种真实的食物饮食的效果，PA和OA的相对浓度不同。 将实现两个具体目标： 1.确定与PA较低和OA高得多的饮食相比，增加饮食中PA含量是否会降低进食状态下的脂肪氧化。 2.确定提高饲料中PA含量是否会增加肌肉的三酰甘油（TAG）和二酰甘油（DAG）含量，并改变肌肉的心磷脂含量、肌肉和脂肪组织中磷脂的脂肪酸组成以及骨骼肌的酰基肉毒碱和酰基辅酶A谱。 该项目将提供非肥胖、非糖尿病人群中PA和OA（饮食中两种最常见的FA）对脂肪氧化和肌肉脂质影响的新数据。 这项研究将对预防胰岛素抵抗、糖尿病和肥胖症具有特别的意义。